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Neurology Jun 2017To estimate the placebo and nocebo responses in restless legs syndrome (RLS) and explore their determinants. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To estimate the placebo and nocebo responses in restless legs syndrome (RLS) and explore their determinants.
METHODS
Databases were searched up to October 2015. Randomized, double-blind, placebo-controlled trials of patients with RLS were included if quantitative data were extractable in the placebo arm. Placebo response was defined as the within-group change from baseline, using any scale measuring RLS severity or disability. Nocebo response was defined as the proportion of patients experiencing adverse events in the placebo arm. Random-effects meta-analysis was used to pool data. Statistical heterogeneity was assessed with statistic. Several predetermined subgroup and sensitivity analysis were performed. PROSPERO registration number is CRD42015027992.
RESULTS
We included 85 randomized controlled trials (5,046 participants). Pooled placebo response effect size was -1.41 (95% confidence interval [CI] -1.56 to -1.25, 64 trials, = 88.1%), corresponding to -6.58 points in the International RLS Study Group Scale (IRLS). Pooled nocebo response was 45.36% (95% CI 40.47%-50.29%, 72 trials; = 89.8%). The placebo and nocebo responses were greater in trials with longer duration, evaluating pharmacologic interventions and idiopathic RLS, and in industry-funded and unpublished studies. The placebo response was considerably smaller in objective as compared to subjective outcomes. In addition, the nocebo response increases proportionally with the placebo response, and has the same predictors.
CONCLUSIONS
The magnitude of the placebo response in RLS is above the threshold of minimal clinical important difference, and the frequency of adverse events is also considerable. These results are relevant to inform the design and interpretation of future clinical trials.
Topics: Humans; Placebo Effect; Randomized Controlled Trials as Topic; Restless Legs Syndrome
PubMed: 28490647
DOI: 10.1212/WNL.0000000000004004 -
Medicine Apr 2016This systematic review was performed to investigate the ethical justification, methodological quality, validity and safety of placebo controls in randomized... (Meta-Analysis)
Meta-Analysis Review
This systematic review was performed to investigate the ethical justification, methodological quality, validity and safety of placebo controls in randomized placebo-controlled surgical trials.Central, MEDLINE, and EMBASE were systematically searched to identify randomized controlled trials comparing a surgical procedure to a placebo. "Surgical procedure" was defined as a medical procedure involving an incision with instruments. Placebo was defined as a blinded sham operation involving no change to the structural anatomy and without an expectable physiological response in the target body compartment.Ten randomized placebo-controlled controlled surgical trials were included, all of them published in high-ranking medical journals (mean impact factor: 20.1). Eight of 10 failed to show statistical superiority of the experimental intervention. Serious adverse events did not differ between the groups (rate ratio [RR] 1.38, 95% confidence interval [CI]: 0.92-2.06, P = 0.46). None of the trials had a high risk of bias in any domain. The ethical justification for the use of a placebo control remained unclear in 2 trials.Placebo-controlled surgical trials are feasible and provide high-quality data on efficacy of surgical treatments. The surgical placebo entails a considerable risk for study participants. Consequently, a placebo should be used only if justified by the clinical question and by methodological necessity. Based on the current evidence, a pragmatic proposal for the use of placebo controls in future randomized controlled surgical trials is made.
Topics: Patient Safety; Placebo Effect; Randomized Controlled Trials as Topic; Surgical Procedures, Operative
PubMed: 27124060
DOI: 10.1097/MD.0000000000003516 -
Annals of Palliative Medicine Jan 2020Acupuncture is a common alternative therapy for clinical treatment of insomnia. As the underlying mechanism is yet unclear, its efficacy is often considered as placebo... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acupuncture is a common alternative therapy for clinical treatment of insomnia. As the underlying mechanism is yet unclear, its efficacy is often considered as placebo effect. To clarify whether acupuncture treatment of insomnia is only due to its placebo effect, a systematic review and a meta-analysis were designed based on the comparison between acupuncture and sham acupuncture.
METHODS
Four English (PubMed, Embase, Web of Science, and The Cochrane Library) and three Chinese (CNKI, VIP, and Wanfang) databases were searched, and the validity of the eligible studies was critically appraised. Thirteen eligible randomized controlled trials of moderate-to-high quality that employed polysomnography (PSG), actigraphy, or self-assessment sleep quality tools were included in the present study. A meta-analysis was conducted using a random-effects model with the Pittsburgh Sleep Quality Index (PSQI) as the primary outcome measure (911 adult patients, 13 trials) for trials investigating the effects of acupuncture as compared to the sham acupuncture. Then, a subgroup analysis was performed to detect the sources of heterogeneity, identify the selection of sham acupuncture methods and different crowd characteristics, and explore its contributions to the total score change of PSQI.
RESULTS
Compared to the sham groups, acupuncture significantly decreased the PSQI score (P<0.0001). A subgroup analysis showed that the selection of sham acupuncture methods did not affect the results of PSQI. A subgroup of two trials with a total of 141 participants with major depressive disorder did not show any significant reductions in total PSQI scores (P=0.11). In addition, a significant difference was detected in the change of Insomnia Severity Index (ISI) scores (362 adult patients, 4 trials) between acupuncture and sham acupuncture (P<0.0001). The PSG and actigraphy data from acupuncture and the sham did not reveal any significant differences in the sleep structure changes.
CONCLUSIONS
Acupuncture treatment of insomnia is efficacious, not because of its placebo effect. For the selection of sham acupuncture, both methods performed similarly in a clinical setting. Moreover, insomnia patients with major depression disorder were not recommended to use only acupuncture treatment.
Topics: Acupuncture Therapy; Humans; Placebo Effect; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders
PubMed: 32005059
DOI: 10.21037/apm.2019.11.15 -
Journal of Crohn's & Colitis May 2016Minimisation of the placebo responses in randomised controlled trials [RCTs] is essential for efficient evaluation of new interventions. Placebo rates have been high in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Minimisation of the placebo responses in randomised controlled trials [RCTs] is essential for efficient evaluation of new interventions. Placebo rates have been high in ulcerative colitis [UC] clinical trials, and factors influencing this are poorly understood. We quantify placebo response and remission rates in UC RCTs and identify trial design factors influencing them.
METHODS
MEDLINE, EMBASE, and the Cochrane Library were searched from inception through April 2014 for placebo-controlled trials in adult patients with UC of a biological agent, corticosteroid, immunosuppressant, or aminosalicylate. Data were independently doubly extracted. Quality was assessed using the Cochrane risk of bias tool.
RESULTS
In all, 51 trials [48 induction and 10 maintenance phases] were identified. Placebo response and remission rates were pooled according to random-effects models, and mixed-effects meta-regression models were used to evaluate effects of study-level characteristics on these rates. Pooled estimates of placebo remission and response rates for induction trials were 10% (95% confidence interval [CI] 7-13%) and 33% [95% CI 29-37%], respectively. Corresponding values for maintenance trials were 19% [95% CI 11-30%] and 22% [95% CI 17-28%]. Trials enrolling patients with more active disease confirmed by endoscopy [endoscopy subscore ≥ 2] were associated with lower placebo rates. Conversely, placebo rates increased with increasing trial duration and number of study visits.
CONCLUSIONS
Objective assessment of greater disease activity at trial entry by endoscopy lowered placebo rates, whereas increasing trial duration and more interactions with healthcare providers increased placebo rates. These findings have important implications for design and conduct of clinical trials.
Topics: Anti-Inflammatory Agents; Colitis, Ulcerative; Humans; Immunosuppressive Agents; Induction Chemotherapy; Maintenance Chemotherapy; Models, Statistical; Placebo Effect; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome
PubMed: 26746169
DOI: 10.1093/ecco-jcc/jjw004 -
European Journal of Sport Science Apr 2020The aim of this review was to determine the magnitude of the placebo and nocebo effect on sport performance. Articles published before March 2019 were located using...
The aim of this review was to determine the magnitude of the placebo and nocebo effect on sport performance. Articles published before March 2019 were located using Medline, Web of Science, PubMed, EBSCO, Science Direct, and Scopus. Studies that examined placebo and nocebo effects of an objective dependent variable on sports performance, which included a control or baseline condition, were included in the analysis. Studies were classified into two categories of ergogenic aids: (1) nutritional and (2) mechanical. Cohen's effect sizes were calculated from 32 studies involving 1513 participants. Small to moderate placebo effects were found for both placebo ( = 0.36) and nocebo ( = 0.37) effects and when separated by nutritional ( = 0.35) and mechanical ( = 0.47) ergogenic aids. The pooled effect size revealed a small to moderate effect size across all studies ( = 0.38). Results suggest that placebo and nocebo effects can exert a small to moderate effect on sports performance.
Topics: Athletic Performance; Dietary Supplements; Humans; Nocebo Effect; Performance-Enhancing Substances; Placebo Effect; Transcutaneous Electric Nerve Stimulation
PubMed: 31414966
DOI: 10.1080/17461391.2019.1655098 -
The Cochrane Database of Systematic... Aug 2021This is an updated Cochrane Review, first published in 2006 and updated in 2014. Gout is one of the most common rheumatic diseases worldwide. Despite the use of... (Review)
Review
BACKGROUND
This is an updated Cochrane Review, first published in 2006 and updated in 2014. Gout is one of the most common rheumatic diseases worldwide. Despite the use of colchicine as one of the first-line therapies for the treatment of acute gout, evidence for its benefits and harms is relatively limited.
OBJECTIVES
To update the available evidence of the benefits and harms of colchicine for the treatment of acute gout.
SEARCH METHODS
We updated the search of CENTRAL, MEDLINE, Embase, Clinicaltrials.gov and WHO ICTRP registries to 28 August 2020. We did not impose any date or language restrictions in the search.
SELECTION CRITERIA
We considered published randomised controlled trials (RCTs) and quasi-randomised controlled trials (quasi-RCTs) evaluating colchicine therapy compared with another therapy (placebo or active) in acute gout; low-dose colchicine at clinically relevant doses compared with placebo was the primary comparison. The major outcomes were pain, participant global assessment of treatment success (proportion with 50% or greater decrease in pain from baseline up to 32 to 36 hours), reduction of inflammation, function of target joint, serious adverse events, total adverse events and withdrawals due to adverse events.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by Cochrane in this review update.
MAIN RESULTS
We included four trials (803 randomised participants), including two new trials, in this updated review. One three-arm trial compared high-dose colchicine (52 participants), low-dose colchicine (74 participants) and placebo (59 participants); one trial compared high-dose colchicine with placebo (43 participants); one trial compared low-dose colchicine with non-steroidal anti-inflammatory drugs (NSAIDs) (399 participants); and one trial compared low-dose colchicine with Chuanhu anti-gout mixture (traditional Chinese Medicine compound) (176 participants). We did not identify any trials comparing colchicine to glucocorticoids (by any route). The mean age of participants ranged from 51.2 to 70 years, and trial duration from 48 hours to 12 weeks. Two trials were at low risk of bias, one was possibly susceptible to selection bias (random sequence generation), reporting bias and other bias, and one open-label trial was at high risk of performance and detection bias. For the primary comparison, low-quality evidence from one trial (103 participants, downgraded for imprecision and bias) suggests low-dose colchicine may improve treatment outcome compared to placebo with little or no increased risk of adverse events. The number of people who reported treatment success (50% or greater pain reduction) at 32 to 36 hours was slightly larger with low-dose colchicine (418 per 1000) compared with placebo (172 per 1000; risk ratio (RR) 2.43, 95% confidence interval (CI) 1.05 to 5.64; absolute improvement 25% more reported success (7% more to 42% more, the 95% CIs include both a clinically important and unimportant benefit); relative change of 143% more people reported treatment success (5% more to 464% more). The incidence of total adverse events was 364 per 1000 with low-dose colchicine compared with 276 per 1000 with placebo: RR 1.32, 95% CI 0.68 to 2.56; absolute difference 9% more events with low-dose colchicine (9% fewer to 43% more, the 95% CIs include both a clinically important effect and no effect); relative change of 32% more events (32% fewer to 156% more). No participants withdrew due to adverse events or reported any serious adverse events. Pain, inflammation and function were not reported. Low-quality evidence (downgraded for imprecision and bias) from two trials (124 participants) suggests that high-dose colchicine compared to placebo may improve symptoms, but with increased risk of harms. More participants reported treatment success at 32 to 36 hours with high-dose colchicine (518 per 1000) compared with placebo (240 per 1000): RR 2.16, 95% CI 1.28 to 3.65, absolute improvement 28% (8% more to 46% more); more also had reduced inflammation at this time point with high-dose colchicine (504 per 1000) compared with placebo (48 per 1000): RR 10.50, 95% CI 1.48 to 74.38; absolute improvement 45% greater (22% greater to 68% greater); but more adverse events were reported with high-dose colchicine (829 per 1000 compared with 260 per 1000): RR 3.21, 95% CI 2.01 to 5.11, absolute difference 57% (26% more to 74% more). Pain and function were not reported. Low-quality evidence from a single trial comparing high-dose to low-dose colchicine indicates there may be little or no difference in benefit in terms of treatment success at 32 to 36 hours but more adverse events associated with the higher dose. Similarly, low-quality evidence from a single trial indicates there may also be little or no benefit of low-dose colchicine over NSAIDs in terms of treatment success and pain reduction at seven days, with a similar number of adverse events reported at four weeks follow-up. Reduction of inflammation, function of target joint and withdrawals due to adverse events were not reported in either of these trials, and pain was not reported in the high-dose versus low-dose colchicine trial. We were unable to estimate the risk of serious adverse events for most comparisons as there were few events reported in the trials. One trial (399 participants) reported three serious adverse (one in a participant receiving low-dose colchicine and two in participants receiving NSAIDs), due to reasons unrelated to the trial (low-quality evidence downgraded for bias and imprecision).
AUTHORS' CONCLUSIONS
We found low-quality evidence that low-dose colchicine may be an effective treatment for acute gout when compared to placebo and low-quality evidence that its benefits may be similar to NSAIDs. We downgraded the evidence for bias and imprecision. While both high- and low-dose colchicine improve pain when compared to placebo, low-quality evidence suggests that high-dose (but not low-dose) colchicine may increase the number of adverse events compared to placebo, while low-quality evidence indicates that the number of adverse events may be similar with low-dose colchicine and NSAIDs. Further trials comparing colchicine to placebo or other treatment will likely have an important impact on our confidence in the effect estimates and may change the conclusions of this review. There are no trials reporting the effect of colchicine in populations with comorbidities or in comparison with other commonly used treatments, such as glucocorticoids.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Child, Preschool; Colchicine; Glucocorticoids; Gout; Humans; Infant; Pain
PubMed: 34438469
DOI: 10.1002/14651858.CD006190.pub3 -
Medicine Aug 2016Placebo, defined as "false treatment," is a common gold-standard method to assess the validity of a therapy both in pharmacological trials and manual medicine research... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Placebo, defined as "false treatment," is a common gold-standard method to assess the validity of a therapy both in pharmacological trials and manual medicine research where placebo is also referred to as "sham therapy." In the medical literature, guidelines have been proposed on how to conduct robust placebo-controlled trials, but mainly in a drug-based scenario. In contrast, there are not precise guidelines on how to conduct a placebo-controlled in manual medicine trials (particularly osteopathy). The aim of the present systematic review was to report how and what type of sham methods, dosage, operator characteristics, and patient types were used in osteopathic clinical trials and, eventually, assess sham clinical effectiveness.
METHODS
A systematic Cochrane-based review was conducted by analyzing the osteopathic trials that used both manual and nonmanual placebo control. Searches were conducted on 8 databases from journal inception to December 2015 using a pragmatic literature search approach. Two independent reviewers conducted the study selection and data extraction for each study. The risk of bias was evaluated according to the Cochrane methods.
RESULTS
A total of 64 studies were eligible for analysis collecting a total of 5024 participants. More than half (43 studies) used a manual placebo; 9 studies used a nonmanual placebo; and 12 studies used both manual and nonmanual placebo. Data showed lack of reporting sham therapy information across studies. Risk of bias analysis demonstrated a high risk of bias for allocation, blinding of personnel and participants, selective, and other bias. To explore the clinical effects of sham therapies used, a quantitative analysis was planned. However, due to the high heterogeneity of sham approaches used no further analyses were performed.
CONCLUSION
High heterogeneity regarding placebo used between studies, lack of reporting information on placebo methods and within-study variability between sham and real treatment procedures suggest prudence in reading and interpreting study findings in manual osteopathic randomized controlled trials (RCTs). Efforts must be made to promote guidelines to design the most reliable placebo for manual RCTs as a means of increasing the internal validity and improve external validity of findings.
Topics: Controlled Clinical Trials as Topic; Humans; Osteopathic Medicine; Placebo Effect
PubMed: 27583913
DOI: 10.1097/MD.0000000000004728 -
Sleep Medicine Reviews Apr 2018This systematic review and meta-analysis aimed to determine the size of the placebo effect for insomnia symptoms when comparing placebo treatment with no treatment.... (Review)
Review
This systematic review and meta-analysis aimed to determine the size of the placebo effect for insomnia symptoms when comparing placebo treatment with no treatment. PsycINFO, MEDLINE, and CINAHL databases were systematically searched for studies allocating participants with insomnia symptoms (diagnosed or self-reported) to receive a placebo that they were led to believe was an active treatment or to a no treatment control group. Thirteen independent studies (n = 566) met inclusion criteria. Meta-analysis indicated a reliable placebo effect whereby placebo treatment led to improved perceived sleep onset latency (SOL; Hedges g = 0.272), total sleep time (TST; Hedges g = 0.322), and global sleep quality (GSQ; Hedges' g = 0.581), when compared with no treatment. There was no effect on objective assessment of SOL, however only a few studies reported this outcome and there were insufficient sample sizes to meta-analyse other objective outcomes. Moderator analysis indicated that the placebo effect for perceived insomnia symptoms was quite consistent across different variables. The present findings provide strong evidence for placebo effects for perceived insomnia symptoms, but not on the only objective measurement with sufficient sample size to meta-analyse, namely objective SOL. This has important implications for the treatment of insomnia symptoms and the design and interpretation of clinical trials for insomnia symptoms.
Topics: Humans; Placebo Effect; Self Report; Sleep; Sleep Initiation and Maintenance Disorders
PubMed: 28554719
DOI: 10.1016/j.smrv.2017.03.006 -
Journal of Cosmetic Dermatology Oct 2023To assess the effect and safety of probiotics for treating urticaria. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To assess the effect and safety of probiotics for treating urticaria.
METHODS
Randomized controlled trial (RCT) papers on the probiotics treatment published before May 2019 were retrieved from various databases like PubMed, EMbase, MEDLINE (Ovid), SCI-Hub, Springer, ClinicalKey, VIP, and CNKI. The treatment plan that we include are oral administration of single probiotic, multiple probiotics, and the combination of probiotics and antihistamines. Meta-analysis of the data was performed by RevMan 5.3 software.
RESULTS
A total of nine RCT papers were included: four papers for oral administration of single probiotic, three papers for oral administration of multiple probiotics, and two papers for oral administration of a probiotic combined with antihistamines. The results of meta-analysis showed that the therapeutic effect of the probiotic group was significantly higher than the control group (placebo or antihistamines) (RR = 1.09, 95% CI: 1.03-1.16, p = 0.006). And compared with the placebo group, the therapeutic effect of single probiotic group was significantly improved (RR = 1.11, 95% CI: 1.01-1.21, p = 0.03). Regarding therapeutic effect, there was no statistically significant difference between the multiple probiotics group and placebo group (RR = 1.00, 95% CI: 0.94 ~ 1.07, p = 0.91); the therapeutic effect of single probiotic combined antihistamine group was significantly higher than the antihistamine group (RR = 1.13, 95% CI: 1.07-1.19, p < 0.0001). Regarding the incidence of adverse reactions, there was no significant difference between the probiotic group and the control group (p = 0.46).
CONCLUSION
The treatment plan of oral administration of probiotics has significant therapeutic effects on urticaria, but the therapeutic effects of the administration of multiple probiotics and the safety of probiotic therapy are still not yet obvious. Some large-scale, multi-centered RCT studies are needed in the future for clarification.
Topics: Humans; Probiotics; Administration, Oral; Histamine H1 Antagonists; Urticaria
PubMed: 37221968
DOI: 10.1111/jocd.15782 -
British Journal of Clinical Pharmacology Feb 2021The aim of this systematic review was to explore and evaluate the efficacy of interventions to reduce the prevalence of look-alike, sound-alike (LASA) medication name... (Review)
Review
AIMS
The aim of this systematic review was to explore and evaluate the efficacy of interventions to reduce the prevalence of look-alike, sound-alike (LASA) medication name errors.
METHODS
We conducted a systematic review of the literature, searching PubMed, EMBASE, Scopus and Web of Science up to December 2016, and re-ran the search in February 2020 for later results. We included studies of interventions to reduce LASA errors and included randomized controlled trials, controlled before-and-after studies, and interrupted time series. Details were registered in Prospero (ID: CRD42016048198).
RESULTS
We identified six studies that fulfilled our inclusion criteria. All were conducted in laboratories. Given the diversity in the included studies, we did not conduct a meta-analysis and instead report the findings narratively. The only intervention explored in RCTs was capitalization of selected letters ("Tall Man"), for which we found limited efficacy and no consensus.
CONCLUSIONS
Tall Man lettering is a marginally effective intervention to reduce LASA errors, with a number of caveats. We suggest that Tall Man gives rise to a "quasi-placebo effect", whereby a user derives more benefit from Tall Man lettering if they are aware of its purpose.
Topics: Consensus; Humans; Interrupted Time Series Analysis; Male; Medication Errors
PubMed: 33197079
DOI: 10.1111/bcp.14644